Emotional Homeostasis Research Articles

A technology for providing therapeutic training of children with the anxiety-depressive disorders, comorbid with obesity

Background and aimsThe study considers the problem of the anxiety-depressive disorders (ADD) in children with concomitant obesity in the context of the search for effective methods of their correction.Materials and methodsIncluded 64 children at puberty with the anxiety-depressive disorders, comorbid with obesity. Design comprised: clinicopsychopathological, somatoneurological, psychological monitoring (CDRS-R); the Spielberger, “Me and my illness” and “Man in the Rain” projective drawing tests.ResultsThe symptoms of emotional and vegetative tension, depression registered in all studied children.In the developed model of support, the interventions of primary level are aimed on family and closest encirclement of the child (family psychotherapy, psycho-educational programs for children and their parents). Strategies:– stressful situation in the family (practical, psychological support and education of parents);– for relief of depressive and vegetative-anxious symptoms (using art therapy, cognitive behavioral therapy);– for education of patients in the wider context – quality of life, coping, motivation and modification of inappropriate behaviors (modeling of new cognitions).The technology includes the diagnosis of the psychosomatic core of the disease, areas of neurotic fixation of the child with ADD and obesity, correction of emotional homeostasis and cognitive imbalance by activation of the personality individual resources as a result using cognitive-behavioral and art-dynamic therapy, as well as a “Control of eating behavior” training program, and solving certain situational problems by a child with the disease.ConclusionOur method makes the tactics of psychotherapeutic and psycho-educational intervention at an early stage of the disease.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Actitudes disfuncionales en pacientes con trastorno grave de personalidad: inespecificidad sintomatológica y cambio

The frequent co-occurrence of affective and personality disorders (PD) is associated with poor prognosis. We examined the role of dysfunctional attitudes (DA) in this interaction, analysing different self-reporting variables in people with a diagnosis of PD (n=262) with and without depression. We found no differences by age, sex, or therapeutic adherence; DA are associated with depressive symptoms, general and PD severity, pathological traits (especially borderline and self-destructive, with d> 0.80) and, in the opposite way, with self-efficacy, self-esteem, and social competence. Those who manage to reverse DA after 6 months’ intervention (37.4%) also obtained a better outcome. A non-linear perspective may help explain the complex interaction between the increased sense of personal and interpersonal agency (preparing behavioural change), DA (cognitive schemata), and the preservation of well-being (emotional homeostasis).

The effects anandamide signaling in the prelimbic cortex and basolateral amygdala on coping with environmental stimuli in rats

Several lines of recent evidence suggest that endocannabinoids affect behavior by influencing the general patterns of challenge responding. Here, we investigated the brain mechanisms underlying this phenomenon in rats. The anandamide hydrolysis inhibitor URB597 was condensed into the tip of stainless steel cannulae, which were chronically implanted slightly above the prelimbic cortex (PRL) or the basolateral amygdala (BLA), two important regions of coping and endocannabinoid action. Thereafter, we investigated behavioral responsiveness to ambient light level in the elevated plus-maze and conditioned fear tests. URB597 concentration was ~30μg/mg protein in target areas; local brain anandamide levels increased threefold, without significant changes in 2-arachidonoylglycerol. High levels of illumination halved the time spent by controls in the open arms of the plus-maze. No similar decrease was observed in rats with URB597 implants in the PRL. High light decreased conditioned fear by 30% in controls, but not in rats with prelimbic URB597 implants. Unresponsiveness to environmental challenges was not attributable to the anxiolytic effects of anandamide enhancement, as implants induced paradoxical anxiogenic-like effects under low light, which could be explained by effects on stimulus responsiveness rather than by effects on anxiety. URB597 implants targeting the BLA did not affect stimulus responsiveness. Our findings show that elevated prelimbic anandamide signaling leads to less environment-dependent (more autonomous) behavioral responses to challenges, which is an attribute of active coping styles. These findings are discussed in light of two emerging concepts of endocannabinoid roles, particularly "emotional homeostasis" and "active coping."

Modulation of cannabinoid signaling by amygdala α2-adrenergic system in fear conditioning

The noradrenergic system plays a critical role in the modulation of emotional state, primarily related to anxiety, arousal, and stress. Growing evidence suggests that the endocannabinoid system mediates stress responses and emotional homeostasis, in part, by targeting noradrenergic circuits. In addition, there is an interaction between the cannabinoid and noradrenergic system that has significant functional and behavioral implications. Considering the importance of these systems in forming memories for fearful events, we have investigated the involvement of basolateral amygdala (BLA) α2-adrenoceptors on ACPA (as selective cannabinoid CB1 agonist)-induced inhibition of the acquisition of contextual and auditory conditioned fear. A contextual and auditory fear conditioning apparatus for assess fear memory in adult male NMRI mice was used. Pre-training, intraperitoneal administration of ACPA decreased the percentage freezing time in contextual (at doses of 0.05 and 0.1mg/kg) and auditory (at dose of 0.1mg/kg) in the fear conditioning task, indicating memory acquisition deficit. The same result was observed with intra-BLA microinjection of clonidine (0.001–0.5μg/mouse, for both memories), as α2-adrenoceptor agonist and yohimbine (at doses of 0.005 and 0.05 for contextual and at dose of 0.05μg/mouse for auditory fear memory), as α2-adrenoceptor antagonist. In addition, intra-BLA microinjection of clonidine (0.0005μg/mouse) did not alter ACPA response in both conditions, while the same dose of yohimbine potentiated ACPA response at the lower dose on contextual fear memory. It is concluded that BLA α2-adrenergic receptors may be involved in context- but not tone-dependent fear memory impairment induced by activation of CB1 receptors.

Biological substrates of migraine

Migraine episodes are probably originated by central mechanisms in brain areas able to cause the classical neurological symptoms of prodromes and aura. Conversely, the headache phase begins with the activation of meningeal nociceptors at the origin of the trigeminovascular system. Recent information has postulated that the occurrence of aura can activate nociceptors in the meninges. Conversely, the mechanisms by which common prodromes initiate the headache phase or what sequence of events triggers activation of the meningeal nociceptors is not yet understood. However, a mechanistic analysis for a common factor in migraine clinical features strongly suggests a genetic predisposition to generalized neuronal hyperexcitability. Hypothalamic neurons are sensitive to changes in physiological and emotional homeostasis and they might activate meningeal nociceptors by altering the balance between parasympathetic and sympathetic influence in the meninges. Accordingly, hypothalamic neurons that contain dopamine, histamine, and orexin, and brainstem neurons that contain noradrenaline and serotonin send inputs to trigemino-thalamic neurons in sensory thalamic nuclei. These neurotransmitters can shift the activity of thalamic neurons. Clinical and preclinical studies suggest that migraine aura is caused by cortical spreading depression (CSD), a slowly propagating wave of depolarization/excitation followed by inhibition in cortical neurons and glia. In the cortex, the initial membrane depolarization is associated with a large efflux of potassium, influx of sodium and calcium and release of glutamate. Interestingly, endogenous CGRP is released in the cortical tissue during CSD, and CGRP receptor antagonists have an inhibitory effect on CSD, suggesting a critical role of CGRP in this phenomenon. The demonstration that CGRP antagonism reduces CSD supports the possible use of drugs targeting central CGRP receptors as antimigraine agents. Finally, among the various pathophysiological conditions controlling the expression and the features of headache in migraine, medication-overuse headache (MOH) plays a central role. MOH is a clinically important entity and it is now well documented that the regular use of acute symptomatic medication by people with migraine increases the risk of aggravation of the primary headache. MOH is one of the most common causes of chronic migraine-like syndrome. We have analyzed the possible mechanisms underlying sensitization in MOH by comparing these mechanisms with those reported for other forms of drug addiction. Recent data support the evidence for cognitive impulsivity in drug overuse in headache and in other forms of addiction associated with dysfunction of the frontostriatal system and an integrative hypothesis for compulsive reward-seeking in MOH.

Aging and wisdom: age-related changes in economic and social decision making.

World life expectancy is increasing and many populations will begin to age rapidly. The impeding prevalence of a greater number of older people living longer lives will have significant social and economic implications. It is important to understand how older people make economic and social decisions. Aging can be associated with a “phenomenon of decline” and also greater wisdom. This paper seeks to examine the relationship between wisdom and aging. It reviews and connects the behavioral sciences and neuroscience literature on age differences in the following social and economic decision making domains that represent subcomponents of wisdom: (1) prosocial behavior in experimental economic games and competitive situations; (2) resolving social conflicts; (3) emotional homeostasis; (4) self-reflection; (5) dealing effectively with uncertainty in the domains of risk, ambiguity and intertemporal choice. Overall, we find a lack of research into how older people make economic and social decisions. There is, however, some evidence that older adults outperform young adults on certain subcomponents of wisdom, but the exact relationship between old age and each subcomponent remains unclear. A better understanding of these relationships holds the potential to alleviate a wide range of mental health problems, and has broad implications for social policies aimed at the elderly.

Neurochemical pathways that converge on thalamic trigeminovascular neurons: potential substrate for modulation of migraine by sleep, food intake, stress and anxiety.

Dynamic thalamic regulation of sensory signals allows the cortex to adjust better to rapidly changing behavioral, physiological and environmental demands. To fulfill this role, thalamic neurons must themselves be subjected to constantly changing modulatory inputs that originate in multiple neurochemical pathways involved in autonomic, affective and cognitive functions. Our overall goal is to define an anatomical framework for conceptualizing how a ‘decision’ is made on whether a trigeminovascular thalamic neuron fires, for how long, and at what frequency. To begin answering this question, we determine which neuropeptides/neurotransmitters are in a position to modulate thalamic trigeminovascular neurons. Using a combination of in-vivo single-unit recording, juxtacellular labeling with tetramethylrhodamine dextran (TMR) and in-vitro immunohistochemistry, we found that thalamic trigeminovascular neurons were surrounded by high density of axons containing biomarkers of glutamate, GABA, dopamine and serotonin; moderate density of axons containing noradrenaline and histamine; low density of axons containing orexin and melanin concentrating hormone (MCH); but not axons containing CGRP, serotonin 1D receptor, oxytocin or vasopressin. In the context of migraine, the findings suggest that the transmission of headache-related nociceptive signals from the thalamus to the cortex may be modulated by opposing forces (i.e., facilitatory, inhibitory) that are governed by continuous adjustments needed to keep physiological, behavioral, cognitive and emotional homeostasis.

Should we always change bad dietary habits in obese children or not?

That is the question coming out by a psychological point of view, reviewing the cases we have treated in our service recently. Treating childhood obesity with multidisciplinary approach we detected some problems in obese families in term of psychological dynamics frequently. We analyzed cases seen in 2012: 157 people aging mean 11.35 y (sd 3.02), with starting BMI mean 27.28 (sd 4.22); we detected both psychological aspects related to the family and to the child. We found mild-severe problems in 48% of cases in the family area (1) bad quality in relationship between parents (24% infighting with divorced one or being about to separate); (2) severe health problems in families which are able to lead to global emotional distress (38%). Furthermore in term of psycho-physical state we saw in 35% of children evaluated several health evidences in addition to overweight like: dyslexia or specific learning disabilities (26%), behavior diseases (15%), anxiety or emotional distress (24%), tics (5%), migraine (8%); 7% showed neurological pathologies (like cognitive delays) or organic pathologies associated (15%). Binge eating and related obesity seem to be an answer to psychological request in term of emotional distress of the origin familiar unit. So we have really to effort the importance of psychological approach at the same time of nutritional and environmental attention due to young obese patients. Nevertheless we can recommend to value in a very strong way how a radical change could be destabilizing in term of emotional homeostasis when important changes in food habits occur.

The effects of anandamide signaling enhanced by the FAAH inhibitor URB597 on coping styles in rats

Coping styles are fundamental characteristics of behavior that affect susceptibility to, and resilience during, mental and physical illness. Shifts from passive to active coping are considered therapeutic goals in many stress-related disorders, but the neural control of coping is poorly understood. Based on earlier findings, we hypothesized that coping styles are influenced by endocannabinoids. Here, we tested whether FAAH inhibition by URB597 affects behaviors aimed at controlling a critical situation and the degree to which environmental stimuli influence behavior i.e., we studied the impact of URB597 on the two main attributes of coping styles. Rats were tested in the tail-pinch test of coping and in the elevated plus-maze test that was performed under highly divergent conditions. Under the effects of URB597, rats focused their behavior more on the discomfort-inducing clamp in the tail-pinch test, i.e., they coped with the challenge more actively. In the elevated plus-maze, URB597-treated rats demonstrated an autonomous behavioral control by reducing both "wariness" induced by aversive conditions and "carelessness" resulting from favorable conditions. URB597 treatment-induced behavioral changes indicated a shift towards active coping with challenges. This behavioral change appears compatible with the previously suggested role of endocannabinoids in emotional homeostasis. Albeit further studies are required to characterize the role of endocannabinoids in coping, these findings suggest that the enhancement of endocannabinoid signaling may become a therapeutic option in emotional disorders characterized by passive coping (e.g., anxiety and depression) and in physical diseases where active coping is therapeutically desirable.

Emotional, endocrine and brain anandamide response to social challenge in infant male rats

Individual response to stress is orchestrated by hypothalamus-pituitary axis corticosteroids, although critically modulated by the central endocannabinoid (eCB) system. Whilst the role of the eCB system in stress response and emotional homeostasis in adult animals has been extensively studied, it has only been scarcely investigated in developing animals. Herein, we aimed to investigate the participation of eCB ligands in the stress responses of neonate rats. Twelve days-old Wistar male rats were exposed to a social challenge (repeated brief isolations from dam and littermates), which resulted in a significant increase in serum corticosterone levels. This stressful social challenge also decreased spontaneous rat pups' behaviours and augmented isolation-induced ultrasonic vocalizations. Notably, a specific decrease in anandamide content (not 2-AG) was observed within the hippocampus (not in the striatum). However, the enhancement of eCB signalling by URB597 administration (0.1mg/kg) did not affect the adrenocortical and behavioural responses to this postnatal social challenge. The influence of gestational stress was also evaluated in the infant offspring of rats dams exposed to restraint stress (PRS, three episodes/day, on gestation days 14 till delivery); however, PRS did not modify neonate responses to this postnatal challenge. Present findings provide evidence for the participation of the eCB system in the acute response to a social challenge in infant male rats. However, the lack of evidences from the pharmacological study encourages the investigation of alternative and/or indirect mechanisms that may participate in the behavioural and endocrine response to stress in developing animals. Further experiments are still needed to clarify the interactions between the HPA axis and the eCB system in stress reactivity at early postnatal stages.

Defining and Assessing Wisdom: A Review of the Literature

With increasing longevity and a growing focus on successful aging, there has been a recent growth of research designed to operationalize and assess wisdom. We aimed to (1) investigate the degree of overlap among empirical definitions of wisdom, (2) identify the most commonly cited wisdom subcomponents, (3) examine the psychometric properties of existing assessment instruments, and (4) investigate whether certain assessment procedures work particularly well in tapping the essence of subcomponents of the various empirical definitions. We searched PsychINFO-indexed articles published through May 2012 and their bibliographies. Studies were included if they were published in a peer-reviewed journal and (1) proposed a definition of wisdom or (2) discussed the development or validation of an instrument designed to assess wisdom. Thirty-one articles met inclusion criteria. Despite variability among the 24 reviewed definitions, there was significant overlap. Commonly cited subcomponents of wisdom included knowledge of life, prosocial values, self-understanding, acknowledgment of uncertainty, emotional homeostasis, tolerance, openness, spirituality, and sense of humor. Published reports describing the psychometric properties of nine instruments varied in comprehensiveness but most measures were examined for selected types of reliability and validity, which were generally acceptable. Given limitations of self-report procedures, an approach integrating multiple indices (e.g., self-report and performance-based measures) may better capture wisdom. Significant progress in the empirical study of wisdom has occurred over the past four decades; however, much needs to be done. Future studies with larger, more diverse samples are needed to determine the generalizability, usefulness, and clinical applicability of these definitions and assessment instruments. Such work will have relevance for the fields of geriatrics, psychiatry, psychology, sociology, education, and public health, among others.

Frequency shifts in the anterior default mode network and the salience network in chronic pain disorder.

BackgroundRecent functional imaging studies on chronic pain of various organic etiologies have shown significant alterations in both the spatial and the temporal dimensions of the functional connectivity of the human brain in its resting state. However, it remains unclear whether similar changes in intrinsic connectivity networks (ICNs) also occur in patients with chronic pain disorder, defined as persistent, medically unexplained pain.MethodsWe compared 21 patients who suffered from chronic pain disorder with 19 age- and gender-matched controls using 3T-fMRI. All neuroimaging data were analyzed using both independent component analysis (ICA) and power spectra analysis.ResultsIn patients suffering from chronic pain disorder, the fronto-insular ‘salience’ network (FIN) and the anterior default mode network (aDMN) predominantly oscillated at higher frequencies (0.20 - 0.24 Hz), whereas no significant differences were observed in the posterior DMN (pDMN) and the sensorimotor network (SMN).ConclusionsOur results indicate that chronic pain disorder may be a self-sustaining and endogenous mental process that affects temporal organization in terms of a frequency shift in the rhythmical dynamics of cortical networks associated with emotional homeostasis and introspection.

Wisdom: A Qualitative Study Among Hospice Patients

Although the concept of wisdom has been discussed for centuries within the humanities, it has become a current topic of scientific inquiry within aging and psychiatric research. Studies have suggested that wisdom is associated with the lateral prefrontal cortex and the medial prefrontal cortex, areas corresponding to functions of calculated, reason-based decision making and emotional homeostasis as well as pro-social attitudes, respectively. Additionally, six core components of wisdom have been outlined: pro-social attitudes and behavior, social decision making and pragmatic knowledge of life, emotional homeostasis, reflection or self-understanding, value relativism and tolerance, and acknowledgment of and dealing effectively with uncertainty.

A comparison of individual level risk factors for homelessness among older and younger adults: Findings in a homeless sample from Little Rock

homeostasis, reflection or self-understanding, value relativism and tolerance, and acknowledgment of and dealing effectively with uncertainty. These core components offer a roadmap for defining wisdom, and for continuing to explore its determinants and underlying structure. But how does wisdom develop and change over the course of a lifetime? Can wisdom be taught, and if so, what are the necessary characteristics of wisdom? How does adversity affect wisdom? These questions remain unanswered. But elderly adults, particularly those who are facing the end of their lives in hospice care, are well-suited to reflect on these issues. This population is uniquely poised to reflect back on their lives overall, with a prominent awareness of adversity due to their terminal illness. Methods: This study provides a qualitative analysis of hospice patients’ perspectives on the concept of wisdom. A focus is given to patients’ understanding about the definition, characteristics, and development of wisdom, as well as their perspectives on how wisdom has changed throughout their lives as a result of their illness. Furthermore, patients’ responses are compared to the six core components of wisdom as an assessment of the theory’s applicability in this population. Twenty-five hospice patients are completing individualized, semi-structured, qualitative interviews about wisdom. Each patient’s interview, lasting an average of 60 minutes, is being digitally recorded and transcribed. Using grounded theory, each interview is being analyzed and coded by the research team to ascertain the most common emergent themes. Results: Five of the 25 interviews have been completed to date, thereby allowing for preliminary results. Thus far, the most common theme expressed by hospice patients is that wisdom requires learning from mistakes and life experience, with the majority of patients noting their level of wisdom has increased due to their terminal illness. Additionally, patients have most often reported the following characteristics as necessary for wisdom: 1) patience, 2) good communication, and 3) a willingness to self-reflect. When mapping patients’ responses to the six components of wisdom, they have most frequently endorsed the link between wisdom and pro-social attitudes (44%), dealing with uncertainty (20%), and social decision making (19%). Hospice patients have less frequently described a link between wisdom and emotional homeostasis (8%), reflection (8%), or tolerance (1%). Conclusions: The remaining 20 interviews will lead to finalized qualitative analysis for presentation and to a better understanding of how people conceptualize wisdom at the end of their lives.

Homeostatic role of the endocannabinoid system and consequences of its disregulation on emotional states

Homeostatic role of the endocannabinoid system and consequences of its disregulation on emotional states

Targeting the endocannabinoid system to treat haunting traumatic memories

Targeting the endocannabinoid system to treat haunting traumatic memories

1883 – Anxiety personality traits and cannabinoid polymorphisms genes

There is increasing data supporting the role of endocannabinoid system (eCB) in the control of emotional homeostasis, mainly acting through CB1R activation (Menchoulam&Parker, 2012). eCB seems important to maintain baseline anxiety levels and to recovery/adapt to stressful and aversive situations (Moreira&Luz, 2008). A misbalance in eCB system might contribute to the etiology of anxiety related disorders (Crippa et al., 2009; Marco et al., 2012). The cannabinoid receptor 1 (CNR1) gene has been associated to “high neuroticism” and “low agreeableness” phenotype (Juhasz et al., 2009). Study the association between personality traits and genetic polymorphisms located in genes related to eCB ( CNR1, CNR2, FAAH and MGKLL ) in patients with anxiety disorders. In a case-control study, we analyzed 48 polymophisms tagSNPs in sample of 507 Caucasians subjects of both genders. All were assessed using the Semi-Structural Interview of DSM-IV criteria and the Temperament and Character Inventory of Cloninger. Multiple regression analysis was used to determine whether the different personality traits were associated with each variant in CNr1, CNr2, FAAH, and MGKLL , using age and gender as confounder variables. A significant association was found between “high Harm-avoidance” trait and rs1049353 in the CNR1 gene (p< 0.005) and rs1157694 in the FAAH gene (p< 0.001). “Low novelty-seeking” trait was associated with rs324490 in the FAAH gene (p< 0.005). These findings suggest that genetic variations in the CNR1 and FAAH genes may modulate the expression of some clinical aspects of anxiety traits and probably anxiety disorders. Grants: ICIII G03/184; SGR2009/1435 .

The prevalence of metabolic syndrome in drug-naïve bipolar II disorder patients before and after twelve week pharmacological intervention

BackgroundAccumulating evidence indicates a high prevalence rate of metabolic disturbance in bipolar disorder (BP) patients. However, the prevalence across BP subtypes has been investigated to a lesser degree. In the current study, we surveyed the prevalence of metabolic syndrome among drug-naïve bipolar II patients. Moreover, the effects of pharmacological treatment on metabolic indexes were also evaluated. MethodsThis study recruited fifty-six drug-naïve BP II patients diagnosed according to the DSM-IV criteria. Among them, forty-four patients completed a 12-week pharmacological intervention with valproic acid, fluoxetine and lorazepam. Metabolic profiles and body mass index (BMI) were measured at baseline and 2 weeks, 8 weeks, and 12 weeks after receiving medication. ResultsThe mean age of the 56 patients was 30.3±11.1. Before receiving medication, 6.5% of the patients met the ATP III criterion for metabolic syndrome. Among the 44 patients who completed the 12-week pharmacological intervention, the prevalence of metabolic syndrome increased from 7% to 10%. Repeated measurements showed that the changes in metabolic indexes were not significant, with the exceptions of BMI, waist circumference, and buttock circumference. In addition, the interaction between the improvement of hypomanic symptoms and BMI change was significant. LimitationsThe study was limited by the follow-up duration and sample size. ConclusionsIn drug-naïve BP II patients, the prevalence of metabolic syndrome was significantly lower than that observed before in BP I patients. However, medications use was also associated with an increased risk of metabolic disturbance, although the impact was lesser. Clinical evidence suggests that metabolism and emotion homeostasis might share common mechanisms.

Cannabinoid modulation of noradrenergic circuits: Implications for psychiatric disorders

The interaction between the endocannabinoid system and catecholaminergic circuits has gained increasing attention as it is recognized that the development of synthetic cannabinoid receptor agonists/antagonists or compounds targeting endocannabinoid synthesis/metabolism may hold some therapeutic potential for the treatment of psychiatric disorders. The noradrenergic system plays a critical role in the modulation of emotional state, primarily related to anxiety, arousal, and stress. Recent evidence suggests that the endocannabinoid system mediates stress responses and emotional homeostasis, in part, by targeting noradrenergic circuits. This review summarizes our current knowledge regarding the anatomical substrates underlying regulation of noradrenergic circuitry by the endocannabinoid system. It then presents biochemical evidence showing an important effect of cannabinoid modulation on adrenergic receptor signaling. Finally, new evidence from behavioral pharmacology studies is provided demonstrating that norepinephrine is a critical determinant of cannabinoid-induced aversion, adding another dimension to how central noradrenergic circuitry is regulated by the cannabinoid system.

Exposure to Enriched Environment Restores the mRNA Expression of Mineralocorticoid and Glucocorticoid Receptors in the Hippocampus and Ameliorates Depressive-like Symptoms in Chronically Stressed Rats

Chronic stress can cause emotional dysfunction, but exposure to an enriched environment (EE) can benefit emotional homeostasis. Recent studies have demonstrated that EE can ameliorate stress-induced depressive-like behaviors. Whether hypothalamic-pituitary-adrenal (HPA) axis activity and corticosteroid receptors are involved in these effects of EE is not known. In our current study, we examined HPA axis activity and hippocampal mineralocorticoid receptor/glucocorticoid receptor (MR/GR) mRNA levels following chronic stress in rats. Our study showed that stress reduced body weight, decreased sucrose intake and sucrose preference, and increased immobility in a forced swimming test. These effects were ameliorated by EE. Also we found that 21 days of restraint stress resulted in low HPA axis activity, and a reduction of MR mRNA and MR/GR ratio in the hippocampus of rats, which was restored by EE. Thus, our current results emphasizes the efficiency of EE in the amelioration of stress-induced decrease in the mRNA expression of MR and MR/GR ratio as well as behavioral depression, providing initial evidence for a possible mechanism by which an enriched environment can restore stress-induced deficits.